Objective : To investigate the safety and effects of long-term administration of denopamine, β-1 stimulant, on the activities of daily living in heart failure patients.
Design : Case-series.
Methods : One hundred forty patients with mild to moderate chronic heart failure were administered denopamine at dose of 5 to 10 mg three times daily for 24 weeks. Concomitant circulatory system drugs such as digitalis, diuretics, vasodilator drugs, etc., were used without changing the administration method and dose. However, the use of a concomitant β-blocker was prohibited.
Results : Following administration of denopamine, the NYHA cardiac function classification improved by one degree or more in 50 patients (35.7%). The body weight decreased significantly from 54.9± 10.2kg (mean±SD) before administration to 54.0±10.2kg after administration (P<0.05), and the cardiothoracic ratio also decreased from 58.0±7.3% to 56.6±7.2% (P<0.001). No significant changes were observed in the heart rate, systolic blood pressure, or diastolic blood pressure. The activities of daily living improved by one level or more for 49 patients (51.6%). There were 36 withdrawal or dropout cases (patients' own convenience : 12 cases ; complications/accidental symptoms : 7 cases) during the investigation period. Four patients (2.9%) exhibited adverse reactions.
Conclusion : Denopamine seemed to improve the quality of life, which is one of the therapeutic purposes for patients with chronic cardiac failure. A large-scale study including investigation of the long-term prognosis for such patients needs to be performed.

Angiopoietin-1 (Ang1) binds to and activates Tie2 receptor tyrosine kinase. Ang1-Tie2 signal has been proposed to exhibit two opposite roles in the controlling blood vessels. One is vascular stabilization and the other is vascular angiogenesis. There has been no answer to the question as to how Tie2 induces two opposite responses to the same ligand. Our group and Dr. Alitalo's group have demonstrated that trans-associated Tie2 at cell-cell contacts and extracellular matrix (ECM)-anchored Tie2 play distinct roles in the endothelial cells. The complex formation depends on the presence or absence of cell-cell adhesion. Here, we review how Ang1-Tie2 signal regulates vascular maintenance and angiogenesis. We further point to the unanswered questions that must be clarified to extend our knowledge of vascular biology and to progress basic knowledge to the treatment of the diseases in which Ang1-Tie2-mediated signal is central.
Angiopoietin-1/*physiology ; Animals ; Cell Adhesion/physiology ; Cell Movement/physiology ; Endothelial Cells/*physiology ; Endothelium, Vascular/physiology ; Extracellular Matrix/*metabolism ; Humans ; Neovascularization, Physiologic/physiology ; Receptor, TIE-2/*physiology ; Signal Transduction/*physiology